Mutations in chronic myelomonocytic leukemia and their prognostic relevance

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy that overlaps with myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) and tends to transform into acute myeloid leukemia (AML). Among cases of CMML, > 90% have gene mutations, primarily involving TET2 (similar to 60%), ASXL1 (similar to 40%), SRSF2 (similar to 50%), and the RAS pathways (similar to 30%). These gene mutations are associated with both the clinical phenotypes and the prognosis of CMML, special CMML variants and pre-phases of CMML. Cytogenetic abnormalities and the size of genome are also associated with prognosis. Meanwhile, cases with ASXL1, DNMT3A, NRAS, SETBP1, CBL and RUNX1 mutations may have inferior prognoses, but only ASXL1 mutations were confirmed to be independent predictors of the patient outcome and were included in three prognostic models. Novel treatment targets related to the various gene mutations are emerging. Therefore, this review provides new insights to explore the correlations among gene mutations, clinical phenotypes, prognosis, and novel drugs in CMML.

Automated summary

CMML, a hematologic malignancy, often transforms into AML and >90% of cases have gene mutations. These mutations are associated with clinical phenotypes and prognosis, with ASXL1 mutations being an independent predictor and potential therapeutic target.